Chloroethylnitrosoureas (C1EtNUs) kill susceptible human tumor cells by chloroethylation of guanine-06 positions in DNA, leading to the production of interstrand crosslinks. Chloroethylating agents potentially superior to C1EtNUs are being studied. 2-chloroethyl (methylsulfony) methanesulfonate ("C1EtSoSo") (NSC 338947) was found to have the desirable feature of lacking a prominent chemical side-reaction, hydroxyethylation of DNA bases, produced by the C1EtNUs. In reactions with purified DNA, C1EtSoSo produced only chloroethyl products whereas a C1EtNU produced more hydroxyethylation than chloroethyl products. Despite the lack of hyrdroxyethylation reaction, C1EtSoSo is at least as effective as any C1EtNU against experimental tumors. Another chloroethylating agent, mitozolomide, produced a greater diversity of products than did the C1EtNU; this was considered to be an undesirable feature of this drug. The susceptibility of certain human tumor cell lines to C1EtNUs depends on a deficinecy of guanine-06-alkyltransferase. New methods are being developed for isolating this enzyme from human liver and for assaying the enzyme activity in tumor tissues. Studies are in progress to test for relationships between clinical response of malignant glioma patients and DNA crosslinking responses of cells from these patients' tumors to aziridinylbenzoquinone.